Case 5 -

Kayexelate Sorbitol-Induced Bowel Necrosis Laura W. Lamps, M.D. Audrey J. Lazenby, M.D. Joel K. Greenson, M.D.

Clinical Presentation: This 74 year old man was status post right lung lobectomy, with acute decompensation on post-operative day 4. Case 5 - Figure 1 - Mucosal and submucosal necrosis with the resin crystals typical of kayexelate induced bowel necrosis. Case 5 - Figure 2 - Mucosal and submucosal necrosis with the resin crystals typical of kayexelate induced bowel necrosis. Surgical Findings: Grossly necrotic-appearing bowel was resected. Diagnosis : Kayexelate sorbitol -induced bowel necrosis General Comments: One small series and several case reports have documented colonic infarction following the administration of kayexalate-sorbitol enemas. All of the patients had some underlying renal disease, and several were renal transplant patients. The colonic infarction usually presented as the abrupt onset of severe abdominal pain within hours after the administration of the enema. Upon laparatomy and resection, long segments of bowel, and even the entire colon and rectum, were found to be necrotic. Kayexalate is the brand name for sodium polystyrene sulfonate, which is used in the treatment of hyperkalemia. It is a cation-exchange resin with action primarily in the large intestine where the sodium ions are partially released and replaced by potassium. The excess potassium is then evacuated along with the stool. Because kayexalate can cause constipation or even impaction, it is often administered along with an osmotic laxative, usually sorbitol. Sorbitol is a poorly absorbed sugar that is not degraded in the small bowel because the human small intestine lacks enzymes capable of splitting sorbitol into its component monosaccharides. In the colon, however, sorbitol is degraded by colonic bacteria into metabolic products that are acidic and osmotically active. Thus, sorbitol is simply given as an osmotic agent to help expel the kayexalate. Kayexalate and sorbitol are usually administered orally, but for speedier action, both may also be administered as an enema preparation. Pathologic Features: A variety of necro-inflammatory changes have been described including ulcers, pseudomembranes, and transmural necrosis. The necrosis in these cases is bland and maybe mistaken for autolysis save for some hemorrhage and neutrophilic infiltrates. While Kayexalate itself is not known to cause damage, the dark purple crystals of Kayexalate are a useful histologic clue to the possibility that the patient received a sorbitol or other osmotic enema. Thus, in an autopsy or surgically resected specimen with bland colonic infarction and Kayexalate crystals, a phone call to the clinician is warranted, with a discussion of the patient's history. Through such a discussion, the etiology and pathogenesis of a particular patient's colonic ischemia may be elucidated. Most documented cases of Kayexalate-sorbitol injury occur in the colorectum following enemas. Less frequently, damage has been repeated in the upper GI tract following oral administration. Pathogenesis: Following the recognition of these clinical cases, Lillemoe et al investigated the effects of kayexalate-sorbitol enemas in an experimental model using both normal and uremic rats. The results of these experiments are summarized in the following tables. Table 1. Results after enemas in normal (nonuremic) rats Experimental group Colonic pathology No enemas normal Saline enemas normal Kayexalate enemas* normal Sorbitol enemas 7/10 extensive transmural infarction Kayexalate-sorbitol enemas* 6/10 mucosal infarction & focal transmural necrosis Table 2. Results after enemas in uremic rats Experimental group Colonic pathology No enemas normal Saline enemas normal Kayexalate enemas* 1/10 mucosal erythema Sorbitol enemas 9/9 massive dilatation, extensive transmural necrosis Kayexalate-sorbitol enemas all had massive dilatation, extensive transmural necrosis *dark purple crystals of kayexalate noted Two facts are apparent from these experiments: 1) The sorbitol (not the Kayexalate) is responsible for the colonic damage. 2) The damage from sorbitol enemas is potentiated in uremic rats. The detailed pathogenesis of the damage is not known, but it may be speculated that the osmotic load from the sorbitol enemas causes vascular shunting resulting in colonic ischemia. Alternatively, concentrated doses of sorbitol may cause directed toxic damage. Worsening of colonic pathology in the uremic rats is especially interesting, since all of the reported clinical cases have been in patients with severe renal disease. In renal disease, the renin-angiontensin system is disordered with mesenteric vascular instability, and thus the intestinal vasculature of the patients may be particularly vulnerable to an osmotic load. Differential diagnosis: It must be remembered that other resins besides Kayexalate are used clinically. For instance, Questran (cholestyramine) is an orally-administered resin which binds to bile acids in the intestine and is then excreted. It is used in the treatment of hypercholesterolemia, bile-acid induced diarrhea, and C. difficile toxin-induced colitis. The histology of Questran (cholestyramine) is very similar to that of Kayexalate (polystyrene), except that Questran tends to be more opaque. With acid fast stains, Kayexalate crystals are more maroon while Questran is more pink. References: Lillemoe KD, Romolo JL, Hamilton SR, et al. Intestinal necrosis due to sodium polystyrene (Kayexalate) in sorbitol enemas: clinical and experimental support for the hypothesis. Surgery 101 (3):267-272, 1987. Rashid A and Hamilton SR. Necrosis of the gastrointestinal tract in uremic patients as a result of sodium polystyrene sulfonate (Kayexalate) in sorbitol: an underrecognized condition. Am J Surg Pathol 21 (1):60-69, 1997. Scott TR, Graham SM, Schweitzer EJ, Bartlett ST. Colonic necrosis following sodium polystyrene sulfonate (Kayexalate)-sorbitol enema in a renal transplant patient. Report of a case and review of the literature. Dis Colon Rectum 36 (6):607-609, 1993. Wootton FT, Rhodes DF, Lee WM, Fitts CT. Colonic necrosis with Kayexalate-sorbitol enemas after renal transplantation. Ann Intern Med 111 (11): 947-949, 1989.